lecture 6. genes and chromosomes 4 · 2017-03-06 · resume telomerase expression continue to...

GENES AND

CHROMOSOMES IV

Lecture 6 BIOL 266/4

2014-15

Biology Department Concordia University Dr. S. Azam

© 2013 John Wiley & Sons, Inc. All rights reserved.

CELL NUCLEUS AND THE CONTROL OF GENE EXPRESSION


•  DNA and histones are organized into repeating subunits called nucleosomes. •  Each nucleosome includes a

core particle of supercoiled DNA and histone H1 serving as a linker. •  DNA is wrapped around the

core complex. •  The histone core complex

consists of two molecules each of H2A, H2B, H3, and H4 forming an octamer.

Control of Gene Expression in Eukaryotes Chromosomes and Chromatin

H3 H4 H2B

H2A

H3 H2B

Nucleosomal organiza0on of chroma0n: Schema'c diagram (top) and EM of Drosophila cell nucleus with nucleosomes along DNA strand (bo>om)


Control of Gene Expression in Eukaryotes Chromosomes and Chromatin

3D structure of a nucleosome from X-‐ray crystallography. Core par'cle at two views (top) and schema'c of half of a core par'cle (side)


•  A 30-nm filament is another level of chromatin packaging, maintained by histone H1. •  Chromatin filaments

are organized into large supercoiled loops.

Control of Gene Expression in Eukaryotes Higher Levels of Chromatin Structure

30-‐nm fiber: EM of a fiber (leB) and two packaging models (middle, right). © 2013 John Wiley & Sons, Inc. All rights reserved.

1.  Euchromatin (active) returns to a dispersed state after mitosis.

2.  Heterochromatin (inactive) is condensed during interphase. •  Constitutive heterochromatin remains

condensed all the time.   Found mostly around

centromeres and telomeres.   Consists of highly repeated

sequences and few genes. •  Facultative heterochromatin is

inactivated during certain phases of the organism’s life.

Control of Gene Expression in Eukaryotes Heterochromatin and Euchromatin


Control of Gene Expression in Eukaryotes Histone Modification

•  Removal of the acetyl groups from H3 and H4 histones is among the initial steps in conversion of euchromatin heterochromatin.

•  Histone deacetylation is accompanied by methylation of H3K9 by histone methyltransferase in humans.

•  Methylated H3K9 binds to proteins with a chromodomain, for example heterochromatic protein 1 (HP1)

•  Once HP1 is bound to the histone tails, HP1-HP1 interactions facilitate chromatin packaging into a heterochromatin state


Model of possible events during the forma0on of heterochroma0n

Histone deacetylase Histone methyltransferase


Control of Gene Expression in Eukaryotes

Histone Modification

•  Chromatin of a mitotic cell exists in its most highly condensed state.

•  Staining mitotic chromosomes can provide useful information.

•  A karyotype is a preparation of homologous pairs ordered according to size.

•  The pattern on a karyotype may be used to screen chromosomal abnormalities.

Control of Gene Expression in Eukaryotes The Structure of a Mitotic Chromosome


Human mito'c chromosomes labeled with

different specific fluorescent dyes.

The stained chromosomes of a human male arranged in a karyotype

•  Centromere is located at the site markedly indented on a chromosome.

•  Centromeres contain constitutive heterochromatin.

•  Centromeric DNA is the site of microtubule attachment during mitosis.

Control of Gene Expression in Eukaryotes Centromeres


TELOMERE


•  The end of each chromosome is called a telomere and is distinguished by a set of repeated sequences. •  New repeats are added by a

telomerase, a reverse transcriptase that synthesizes DNA from a RNA template. •  Telomeres are required for the

complete replication of the chromosome because they protect the ends from being degraded.

Control of Gene Expression in Eukaryotes Telomeres



Telomerase activity is thought to have major effects on cell life


•  In somatic cells, telomere lengths are reduced after every cell division to limit cell doublings. •  A critical point occurs from

telomere shortening when cells stop their growth and division. •  In contrast, cells that are able to

resume telomerase expression continue to proliferate. •  These cells continue to divide and

do not shown normal signs of aging.

What do you think happens in tumor cells?


Telomerase dynamics during normal and abnormal growth. Limited telomerase levels in soma'c cells

reduces the amount of cell doublings compared to germ cells, unless

telomerase is reac'vated. © 2013 John Wiley & Sons, Inc. All rights reserved.

An Overview of Gene Regulation in Eukaryotes

Cells of a complex eukaryote exist in many differentiated states.

 Differentiated cells retain a full set of genes.

 Nuclei from cells of adult animals are capable of supporting the development of a new individual, as demonstrated in experiments.

Cloning of animals demonstrates that nuclei retain a complete set of genetic information


lecture 6. genes and chromosomes 4 · 2017-03-06 · resume telomerase expression continue to...

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